Collateral blood flow plays a central role during acute ischemic stroke, and the presence of good collaterals has been linked to improved clinical and radiologi- cal outcome measures both with and without successful recanalization. Despite this, the only method to assess adequacy of collaterals currently is in- vasive and expensive, digital subtraction cerebral angiography (DSA). It would be tremendously beneficial if collaterals could be visualized using a tomo- graphic, non-invasive imaging based modality, so that early treatment deci- sions could incorporate this critical information. AIMS AND METHODS The overall goal of the imaging the Collaterals in Acute Stroke (iCAS) study, is to identify and quantify cerebral blood flow (CBF) delivered via collateral routes using arterial spin labeling (ASL), a non-contrast MRI technique, and to determine its impact on ischemic lesion growth and patient outcome. We will perform a prospective, multi-center study of 180 acute stroke patients imaged in the 4.5-12 hr time window with large vessel occlusive stroke who are under consideration for endovascular thrombolytic therapy. We will add two ASL sequences to our rapid stroke protocol: pseudocontinuous ASL (pcASL, 2.5 min) for identifying collaterals and velocity-selective ASL (VS-ASL, 2.5 min) for measuring quantitative CBF independent of arterial arrival delay. In Aim 1, we will demonstrate equivalence between DSA and pcASL for collateral assessment, and determine the relationship between collateral and quantitative CBF using VS-ASL. Then, in Aim 2, we will determine whether ASL might be used to supplement or replace conventional bolus contrast PWI, determine the predictive ability of collateral assessment upon ischemic lesion growth, and evaluate how to incorporate collateral measurements into patient selection algorithms for endovascular therapy by examining the relationship between collaterals, revascularization, and patient outcome. SIGNIFICANCE We believe successful attainment of these aims will markedly improve acute stroke care by validating a non-invasive MRI-based method to assess both the presence of collaterals and the amount of CBF they deliver. iCAS will be the first prospective, multi-center study of ASL, a promising new non-contrast perfusion method, in acute stroke. In particular, the use of VS-ASL to obtain quantitative CBF measurements at serial timepoints in acute stroke will yield invaluable information on this critica hemodynamic parameter. It will provide a framework for incorporating collateral status into treatment decision-making, specifically by answering the question of whether patients with either very good or very poor collaterals benefit from recanalization. This study will lead to bettr understanding of the benefit of ASL measurements in patients with severe cerebrovascular disease and enhance the already significant diagnostic power of MRI in acute ischemic stroke.